Persistent and fast acting antiseptics and disinfectants based on calcium flouride

ABSTRACT

Antiseptic compounds that act as persistent and fast acting antiseptics and disinfectants. The base of these antiseptic actions is CaF 2  as the persistent part, preventing the colonization of tissue and nonliving surfaces with microorganisms through the targeted on-demand release of fluorine ions. For fighting heavy contamination and invasion of transient microbes through new application of the solution, fast acting alcohols and toxic solutions have been added in small percentage. They act fast and evaporate fast, leaving the natural protection of skin undamaged and coated with a persistent antiseptic.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/882,296 filed Sep. 15, 2010, which claims priority of U.S.Provisional Patent Applications Ser. No. 61/242,417 filed Sep. 15, 2009;Ser. No. 61/247,675 filed Oct. 1, 2009; and Ser. No. 61/351,392 filedJun. 4, 2010, which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to antiseptic solution compositions usefulin medical clinical and in public environments for topical and systemicdisinfection.

BACKGROUND OF THE INVENTION

Antiseptics are antimicrobial chemical substances that are applied toliving tissue/skin to reduce the possibility of infection, sepsis orputrefaction caused by microorganisms, and disinfectants destroymicroorganisms found on nonliving objects.

In the second half of the nineteenth century, inspired by LouisPasteur's germ theory of disease, the doctors Lister, Semmelweis,Tichenor and others introduced antiseptic treatment and surgical methodsinto their daily work and initiated a completely new quality ofmedicine: open wounds, surgery, and infectious diseases no longer led topainful death but were cured through topical antiseptics, and later byinternal antibiotics.

Many powerful and fast acting antiseptics have been developed bychemists and applied by doctors and households; some have been abandonedbecause they produced side effects, others because they were just tooinexpensive and not sufficiently profitable to the medical industry; ahandful, mainly alcohol based antiseptics, became standards.

From the beginning Pasteur and his followers stipulated thatdisinfection and antiseptic methods are not 100% effective proceduresand have to be verified and classified using the “killing rate” on thespecific microorganisms reached and attacked by the disinfecting agent.Today we apply “fast acting” and “persistent” topical antiseptics thatall should be “broad spectrum”, i.e. effective against a variety ofmicroorganisms. Fast acting antiseptics are measured by significantreduction in strength determined by cultures obtained a few moments(less than minutes) following application of the antiseptic.

The quality of “persistence” refers to the ability of the antiseptic tocontinue to kill once it is applied and is due to the retention orbinding of the chemical in the stratum corneum of the skin after partialevaporation and after rinsing. It is measured by the time for themicro-flora to be restored to the baseline which existed before theapplication.

Currently there are several fast acting antiseptics, effective within 20seconds against transient microorganisms which could cause infections.Most of these antiseptics are based on alcohols, iodine solutions, orchlorides. However all these fast acting antiseptics cannot prevent fastrepopulation of the depleted (mainly evaporated) “killing ground” wherealso all the natural body protection (fatty acids, different salts,regulated pH 5.4-5.5) against invasions has been destroyed.

Persistence, as applied in food industry or exhibited in ancientembalming practices, has remained an elusive goal of medical antiseptictechnology. Regulating bodies like the FDA have required persistencesince the 1970s for any new antiseptic to be approved, with very littleresponse, actually enhancing the utilization of outdated, nonpersistent,alcohol based disinfectants. Additional regulations for new antisepticsto be tested and evaluated as “medications”, in lengthy and costlyclinical trials, led to an end to all small enterprise chemicaldevelopment and production of innovative disinfectants.

Nature has produced the bill: The surviving microorganisms evolved todevelop resistance to short acting threats that allow them toimmediately recolonize the tissue cleansed by the short persistenceantimicrobials with the next transient flora from the next patient orfrom the next hand grip.

Best practice now requires doctors and care personnel to wash theirhands with antiseptics before and after each patient, X times a day! Thecampaign “Clean Hands” in German hospitals mounted dispenser bottles fordisinfectants on each patient's bed, because the walk to the room's doorand back would add up to miles and hours every day. But the doctors andcaregivers just cannot do it X times a day without heavy damage to theirskin and their health. Compliance therefore remains low and themicroorganisms are “taking over”: In Germany every year some 800,000patients (1 out of 20!) fall seriously ill by in-hospital infections;the number of fatal casualties are kept secret by the hospitalcompanies.

SUMMARY OF THE INVENTION

The present invention is therefore directed to novel antiseptics anddisinfectants which have been designed “bottom up” based on mineralsthat act as persistent “aseptics” and prevent microorganism fromcolonizing nonliving surfaces and skin tissue, while maintaining andeventually enforcing the skin's natural protection flora and mechanisms.

In addition to this persistent preventive action, when heavycontamination and invasion of transient microbes requires a newapplication of the solution, fast acting alcohols and toxic solutionshave been added in small percentage. They act fast on the newmicroorganisms and then evaporate fast, without damaging the naturalprotection of skin and persistent antiseptic.

The compounds of the present invention include:

1) As a base, a natural fine mineral, preferably calcium fluoride(CaF₂), which exhibits a high killing rate on most microorganisms. Thismineral is extremely persistent, sticking to the skin or to surfacepaints for long periods and releasing its killing fluorine ions only “ondemand” when there is moisture and warmth. The mineral is extremelystable, releasing into aqueous solution only 16 mg/l water (=16 ppm) andrebinding immediately when the surface becomes dry again. (CaF₂ is minedunderground in Germany; in some of these mines underground ponds withwater thousands of years old are used as miraculous “fountains of youth”and health baths by the local population.) The CaF₂ is used in a finemilled form with particles in the range of 0.25-5.0 microns andpreferably 0.5-2.5 microns.2) When in solution CaF₂ also releases calcium ions, basic buildingblocks for skin, bones, teeth, and other body tissues, enforcing themagainst any damage and supporting the healing and recovery of cuts,abrasion, and general wounds. This free calcium captures other fluorineions that could be harmful in too high doses.3) CaF₂ has the same pH 5.4 as normal skin (pH 5.4-5.5). It does notdegrade the self-defense mechanisms of the skin, as do soaps.4) Highly toxic and therefore highly efficient antiseptics are added invery low percentage, initiating and amplifying fast antiseptic action onmicroorganisms when newly applied as a wash to the tissue: e.g. 0.2-2.0%Eau de Javel (KClO) or 10% ethanol work well. In medical hand wash theyact fast, then evaporate and release the skin surface with no damage,with the persistent CaF₂ still in place.5) Well known and accepted drugs are added in low percentage, tostabilize and prevent growth of multi-cellular microorganisms like fungiand mildew that are not attacked by the basic CaF₂ ions, thus making thecompound really “broad spectrum”: e.g. 0.6% esters of salicylic acidswork well as fungicide in this compound.

After medical investigation, treatment, or transport, the caregivers canwash their hands X times a day with a new hand wash of these compounds:new transient microbes are killed fast, recolonization is stillprevented by the updated CaF₂+layer.

The following tables show some formulations of the present inventionwith different grade of skin/tissue protection and cure.

EXAMPLE 1 Formulation for CaF₂—Based Antiseptic Spray

Active Agent Mass % mg/l Solubility H₂O (water) 98 980000 CaF₂ (calciumfluoride) 0.005 50 16 ppm Cinnamic acid 0.05 500 high Aspirin ester 0.252500 high Quinic acid 0.1 1000 very high NaOCl (Javel water 2.5%) 0.075750 as ester H₂O₂ (hydrogen peroxide 27%) 1.2 12000 very high Citricacid 0.42 4200 very high

Antimicrobial efficacy of the spray has been improved by adding aspirinester, cinnamic acid, quinic acid, citric acid, and hydrogen peroxideinto very low concentration watery solutions, mixing in CaF₂oversaturated with Javel water, all finally stabilized with citricacids.

The different components act differently and the resulting spray showsexcellent short time action of >log 7 and long time persistency of >log3.

Time 1 Min Time 5 Min Test Microbes [log-grade] [log-grade]Staphylococcus aureus >7.00 >7.00 Pseudomonas aeruginosa >7.26 >7.26Candida albicans >4.87 >4.87 Aspergillus niger >4.61 Duration ComponentMicrobial Efficacy of Effects H₂O (water) none, carrier only CaF₂(calcium bactericide, virucide, fungicide medium to fluoride) extremelong Cinnamic acid bactericide, virucide, fungicide short to longAspirin ester bactericide, virucide, fungicide short to long Quinic acidbactericide, virucide, fungicide short to medium NaOCl (Javel water)bactericide, virucide, fungicide short to medium H₂O₂ (hydrogenbactericide, virucide, fungicide short peroxide) Citric acidbactericide, virucide, fungicide short to medium short = within 60 secup to max 5 min medium = over 5 min up to 1 hour long = over 1 hour upto 4 hours extreme long = over 4 hours

Toxicology Data Acute Toxicology of Active Components:

In Application LD 50 Oral on Component mg/l [mg/3 ml] Rats [mg/kg] CaF₂(calcium fluoride) 50 0.15 4500 Cinnamic acid 500 1.5 2500 Aspirin ester2500 7.5 200 Quinic acid 1000 3.0 >8000 NaOCl (Javel water) 750 2.252000 H₂O₂ (hydrogen peroxide) 12000 36 2000 Citric acid 4000 12.6 3000Permitted toxicity levels for all agents are far above actualapplication. The product will never have toxic effects in humans, evennot in repeated use.On the skin: NO irritationAllergization: NO allergizations reported.

Natural Origins of Active Agents for Disinfection and Medical Cosmetics

Agent Origins Calcium fluoride from the mountains: as mineral fluorsparCinnamic acid from plants: barks, flowers, tanning agents cinnamon,aniseed, chamomile Aspirin ester from plants: barks, tanning agentswillow tree, bamboo, ribwort Quinic acid from plants: barks, flowers,tanning agents cinchona bark, stinging nettles cranberry, blueberry,generally from the fruits of a lot of shrubs Citric acid from plants:pins of most pinewoods citrus, berries, fruits, mushrooms Alginate fromthe sea: brown alga crust Sea salt from the sea: e.g. from the Dead Sea

EXAMPLE 2 Formulation for CaF₂-Based Wound Gel (1000 g)

Alginate 23 g  2.3% skin/tissue cure Salicylic acid ester 6 g 0.6%fungicide Ethanol 20 g  2.0% log 6, fast acting CaF₂ 5 g 0.5% log 3,persistent CaSO₄ 3 g 0.3% skin/tissue cure Pure water 944 g  99.4%

EXAMPLE 3 Formulation for CaF₂-Based Hair Gel (1000 g)

Alginate 17 g  1.7% skin/tissue cure Salicylic acid ester 6 g 0.6%fungicide Isopropyl alcohol 13 g  1.3% log 6, fast acting CaF₂ 5 g 0.5%log 3, persistent CaSO₄ 2 g 0.2% skin/tissue cure Pure water 957 g 95.7%

EXAMPLE 4 Formulation for CaF₂-Based Medical Hand Disinfection Spray(1000 g)

Alginate 3 g 0.3% skin/tissue cure Salicylic acid ester 6 g 0.6%fungicide Ethanol (pharma grade) 100 g  10.0% log 6, fast acting Javelwater 8 g 0.8% log 6, fast acting CaF₂ 3 g 0.3% log 3, persistent CaSO₄1 g 0.1% skin/tissue cure Pure water 879 g  87.9%

The persistent antiseptics of the present invention may be used in avariety of forms. For example, the compounds may be added to paint,varnish, plaster, or gypsum to produce structural surfaces havingantiseptic and/or fungicidal properties. They may be produced inconventional gel or cream form providing their antisepticinfection-preventing properties in a manner for easy application to theskin. They may be added to common alginate containing components likecalcium alginate to produce medical healing and curing creams for openskin wounds or dry skin. They may be added to aqueous gels to producehair care compounds which act as protection against dryness, roughsurface, and microbes. They may be mixed with water and a smallpercentage of alcohol for use in an automatic dispenser or nebulizer.They may be mixed with latex solutions for use in outdoor applicationssuch as spraying fruit trees against blight. They may be mixed withdrinking water for provision to animals which are otherwise easilyinfested by microbes, such as European honeybees. They may be applied torubber and polymer as a filler or sealing agent for use in such productsas handgrips and handlebars, elevator handrails, and the like, therebyproviding persistent protection against bacterial proliferation.

Having thus described our invention, we claim:
 1. An antiseptic compoundformulation for topical application to human and animal skin, comprisingas base a natural mineral from the group of fluorides.
 2. The compoundof claim 1 comprising CaF₂ in its natural form as fine powder fluorspar.3. The compound of claim 2 wherein the fluorspar powder has a finenessof 0.25-5.0 microns.
 4. The compound of claim 2 wherein the fluorsparpowder has a fineness of 0.5-2.5 microns.
 5. The antiseptic compound ofclaim 1 further comprising antiseptics chosen from the group comprisingalcohol, iodine, or chlorine.
 6. The antiseptic compound of claim 3further comprising fungicide drugs.
 7. The antiseptic compound of claim4 further comprising esters of salicylic acid.
 8. The antisepticcompound of claim 4 added to the group comprising paint, varnish,plaster, or gypsum.
 9. The antiseptic compound of claim 4 in the form ofa gel.
 10. The antiseptic compound of claim 4 added to alginatecontaining components.
 11. The antiseptic compound of claim 4 added toaqueous gels to be used as protection against dryness, rough surface andmicrobes in daily hair care and professional hairdressing.
 12. Theantiseptic compound of claim 4 mixed with water and alcohol to be usedin an automatic dispenser.
 13. The antiseptic compound of claim 4 mixedwith some sticking latex solution.
 14. The antiseptic compound of claim4 mixed with drinking water for digestion by animals.
 15. Thedisinfecting compound of claim 3 applied to rubber and polymer as afiller or sealing agent.